Achondroplasia

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Achondroplasia

• AHMG Fall 2004
• Juniata College

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Normal Growth

• Final adult stature is at least 80
  genetic---POLYGENIC
• Birth length20
• Growth
• 1st year10
• 2nd year5
• Thereafter 2.5 per year until puberty
• Final adult height
• Mid-parental height 2 for boys and -2 for girls

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Short stature
Normal or variant short stature
Pathologic short stature
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Short stature
Normal or variant short stature
Pathologic short stature
Genetic short stature
Constitutional delay (i.e. late bloomer) keep
growing when others stop
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Short stature
Normal or variant short stature
Pathologic short stature
Disproportionate short stature ex skeletal
dysplasia Metabolic bone disease Dwarf
Proportionate short stature ex endocrine
problems, Down Syndrome Midget
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Disproportionate short stature diagnosis

• Upper/lower ratio (head to hip socket is upper)
• 1.7 at birth
• 0.95 caucasian adult/0.85 Af. Am. Adult
• Span (fingertip to fingertip)
• Equals height up to adolescence
• After, up to 5 cmheight
• X-rays are diagnostic for skeletal dysplasias

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For general characterization

• Compare
• Chronological age
• Height age (height of a person at the 50th
  percentile for their age)
• Bone age (ossification assessed by X-ray)
• If
• BACA, genetic short stature
• BAHA, constitutional delay
• BA

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Achondroplasia

• AD 1/15,000
• Defect in FGFR3 4p16
• Most common non-lethal Sk. Dys.
• 80 new mutations
• Macrocephaly with midface hypoplasia
• Rhizomelic limb shortening
• Normal intelligence, usually

Jorde et al. Medical Genetics. 2nd edition.
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Hypochondroplasia

• Also caused by mutations in FGFR3 milder than
  achrondroplasia
• AD 1/25,000
• Macrocephaly limb shortening
• Adult height 4.5-5.0 ft.
• Normal intelligence

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Thanatophoric dysplasia

• Mutations in the FGFR3 gene
• AD 1/25,000
• Lethal skeletal dysplasia
• More severely affected with same phenotype as
  achondroplasia
• Also, narrow chest with short ribs/telephone
  receiver femurs/flat vertebrae

http//zygote.swarthmore.edu/cell7.html
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Other causes of short stature

• X-linked hypophosphotemic rickets
• X-linked dominant (males more severely
  affected)(disproportionate)
• Turner Syndrome (45,X) (proportionate)
• Laron Dwarfism
• Insensitivity to growth hormone (receptor
  defect)/AR/proportionate S.S./squeaky voice
• Malnutrition
• Chronic disease
• Other endocrine problems